A stent is an endoprosthetic implant, generally tubular in shape, typically having an open or latticed tubular construction which is expandable to be inserted into an anatomical lumen to provide mechanical support to the lumen and to maintain or to re-establish a flow channel within said lumen. Stents are known for use in blood vessels such as the aorta, carotid artery, or coronary artery or arteries, to treat arterial blockage or aneurysm, for example. In additions, stents are known for use in maintaining patency of body lumens or channels besides blood vessels; these include bile duct stents, urethral stents, and the like. As an example, an endovascular stent may be inserted into a blood vessel during angioplasty, and is designed to prevent early collapse of a vessel that has been weakened or damaged by angioplasty. Insertion of endovascular stents has been shown to reduce negative remodeling of the vessel while healing of the damaged vessel wall proceeds over a period of months.
During the healing process, inflammation caused by angioplasty and stent implant injury often causes smooth muscle cell proliferation and regrowth inside the stent, thus partially closing the flow channel, and thereby reducing or eliminating the beneficial effect of the angioplasty/stenting procedure. This process is called restenosis. Blood clots may also form inside of the newly implanted stent due to the thrombotic nature of the stent surfaces, even when biocompatible materials are used to form the stent. While large blood clots may not form during the angioplasty procedure itself or immediately post-procedure due to the current practice of injecting powerful anti-platelet drugs into the blood circulation, some thrombosis is always present, at least on a microscopic level on stent surfaces, and it is thought to play a significant role in the early stages of restenosis by establishing a biocompatible matrix on the surfaces of the stent whereupon smooth muscle cells may subsequently migrate in and proliferate.
Stents can be of a permanent or temporary nature. Temporary stents which are made from biodegradable material may be advantageous, particularly in cases of recurrent vessel narrowing in which it is desirable to insert a subsequent stent at or near the site of initial stent placement, or where a stent is needed only temporarily to counteract post-surgical swelling that may cause obstruction of a bodily lumen, such as obstruction of the urethra after prostate surgery.
Bioabsorbable/Biodegradable/Bioerodible stents are typically made of synthetic polymers that are biocompatible and are broken down by biological means. Biodegradable stents are also known wherein the outer surfaces or even the entire bulk of polymer material is porous. For example, PCT Publication No. WO 99/07308, which is commonly owned with the present application, discloses such stents, and is expressly incorporated by reference herein.
Stents are also known which contain APIs (active pharmaceutical ingredients), which are generally intended to reduce or eliminate thrombosis or restenosis. Such APIs are often dispersed or dissolved in either a durable or biodegradable polymer matrix, which is applied as a coating over at least a portion of the filament surface. After implantation, the API diffuses out of the polymer matrix and preferably into the surrounding tissue.
A variety of agents specifically claimed to inhibit smooth muscle-cell proliferation, and thus inhibit restenosis, have been proposed for release from endovascular stents. Rapamycin (sirolimus), an immunosuppressant reported to suppress both smooth muscle cell and endothelial cell growth, has been shown to have effectiveness against restenosis, when delivered from a polymer coating on a stent (see, for example, U.S. Pat. Nos. 5,288,711 and 6,153,252). Also, PCT Publication No. WO 97/35575 and WO 2003/090684 describe the macrocyclic triene immunosuppressive compound everolimus and related compounds, which have been proposed for treating restenosis. U.S. Pat. No. 6,159,488 describes the use of a quinazolinone derivative; U.S. Pat. Nos. 6,171,609 and 5,716,981 describe the use of paclitaxel (taxol). U.S. Pat. No. 5,288,711 describes the use of both heparin and rapamycin. Tranilast, a membrane-stabilizing agent thought to have anti-inflammatory properties is disclosed in U.S. Pat. No. 5,733,327. As described in U.S. Pat. No. 6,231,600, a mixture of polymer and therapeutic substance can be coated onto the surface of a stent, which is then coated with a second layer of polymer. The first layer may contain polymer mixed with a therapeutic substance and the second layer may contain polymer mixed with heparin. In U.S. Pat. No. 6,939,376, Shulze et al. disclose a stent for inhibiting restenosis, which is comprised of a stent body and a biodegradable drug-release coating which contains poly(D,L-lactide) polymer and an immunosuppressive compound which is eluted with time at the vascular site of injury. U.S. Pat. No. 6,808,536 discloses local delivery of rapamycin or its analogs from an intravascular stent, either directly from tiny micropores or channels in the stent body or mixed or bound to a polymer coating applied on stent, grooves or channels which are smaller in dimension than the stent struts. Also, U.S. Pat. No. 6,904,658 contains reference to the use of a porous plated layer to contain and elute therapeutic drug.
It is difficult to visualize non-metal, polymer based stents because they are radiolucent. Since optimal stent placement requires real time visualization to allow the cardiologist to track the stent in vivo there is a need to increase the radiopacity of non-metallic polymer based stents. Iodinated contrast media is a common type of intravenous radiographic dye containing iodine that enhances the visibility of vascular structures during radiographic procedures.
Present stents vary widely by geometry. Polymer tubular stent blanks are generally injection molded or extruded, and then die-cut, machined, or laser-cut into the desired geometry or openwork. Alternatively, rolling one or more sheets of metals or polymer may form tubular metal or polymer stent blanks. Stents may also be composed of extruded polymer filaments that are woven into a braid-like structure (see U.S. Pat. No. 6,368,346). To achieve the reticular or openwork nature of the stent body, stents generally comprise radially expandable tubular elements or “bands” which often have a zigzag or sinusoidal structure and which are interconnected by linking elements or “linkers” that typically run in a generally longitudinal direction.
Steinke (U.S. Pat. No. 6,623,521) discloses a locking stent, which may be degradable. The stent is formed from a flat sheet, or sheets, of metal or plastic and bears sliding and locking radial elements or struts. The radial elements may bear a ratcheting mechanism that permits one-way sliding of the radial elements.
U.S. Pat. No. 6,022,371 (Killion) discloses a continuous circumference tubular stent with a unitarily formed locking arm that selectively locks the stent at a desired diameter.
U.S. Pat. No. 6,540,777 (Stenzel) discloses a stent comprising a plurality of interconnected cells, at least one of which is a lockable cell with a first and second locking member which may lock with one another. Also disclosed is a stent comprising a plurality of interconnected bands with a pincer locking member extending toward an adjacent band having a tongue locking member.
U.S. Pat. No. 6,156,062 (McGuinness) discloses a stent comprising a strip of material with a groove along one edge and a tongue along the other edge, to maintain a helical configuration. No locking mechanism is disclosed.
Application Ser. No. U.S. 2004/0249442A1 (Fleming) discloses a stent comprising a lattice having a closed and an open configuration. The lattice is composed of hoops or struts that interlock with one another while moving from a closed to an open configuration, and the hoops interlock with one another by means of teeth on the struts.
U.S. Pat. No. 6,368,346 (Jadhav) discloses biocompatible and biodegradable stents made of blended polymers.
U.S. Pat. No. 5,441,515 (Khosravi) discloses a ratcheting stent comprising a cylindrical sheet having overlapping edges that interlock. The stent may be biodegradable and may be drug-releasing.
U.S. Pat. Nos. 5,817,328 and 6,419,945 disclose buffered resorbable internal fixation polymer devices for bone repair.
U.S. Pat. No. 6,932,930 discloses method to make synthetic polymer strong for stent application.
Unlike traditional metal stents, biodegradable stents are capable of bulk loading of multiple APIs and are temporary implants. Biodegradable stents, however, have typically suffered from insufficient mechanical strength and/or undesirable physical/mechanical elastic polymer recoil. In addition, the degradation time of such stents has been uncontrolled, being dependent mainly on the molecular weight of the polymer resin used. The present stents and methods provide means to adjust the polymer degradation rate and/or to enhance the mechanical strength of the polymer tube or fiber used for biodegradable stent fabrication.